Potassium Phosphate, Tribasic → 3-Cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione

HRID 1891270노트

반응식

HRID 1891270 반응식
Br[C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][C:10](=[O:12])[N:9]([CH:13]3[CH2:15][CH2:14]3)[C:8]2=[O:16])=[CH:4][CH:3]=1.[CH:19]1([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27](B4OC(C)(C)C(C)(C)O4)[CH:28]=3)[C:23]2=[O:40])[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:13]1([N:9]2[C:10](=[O:12])[CH2:11][N:7]([CH2:6][C:5]3[CH:17]=[CH:18][C:2]([C:27]4[CH:28]=[C:29]5[C:24](=[CH:25][CH:26]=4)[C:23](=[O:40])[N:22]([CH:19]4[CH2:21][CH2:20]4)[CH2:30]5)=[CH:3][CH:4]=3)[C:8]2=[O:16])[CH2:15][CH2:14]1

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 66813314HCID 66813314, 화합물

생성물 1

HCID 529323943-Cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione수율 53.1%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

1-(4-bromobenzyl)-3-cyclopropylimidazolidine-2,4-dione (7H5) (0.1 mmol, 30 mg), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.1 mmol, 31.0 mg), tris(dibenzylidineacetone)dipalladium (0.005 mmol, 4.59 mg), tricyclohexylphosphine (0.012 mmol, 3.37 mg) and potassium phosphate (0.17 mmol, 36.1 mg) were suspended in dioxane (1 ml) and water (0.5 ml) and heated to 130° C. in the microwave for 15 min. The reaction mixture was quenched with 2 ml of water and 3 ml of DCM and the organic phase separated using a hydrophobic fritted tube. The organic phase was concentrated and the residue purified by prep basic HPLC to give 3-cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione (Example 7a) 21.3 mg (53%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.63 (d, 1H) 7.58 (m, 3H) 7.35 (d, 2H) 4.59 (s, 2H) 4.37 (s, 2H) 3.71 (s, 2H) 2.96 (m, 1H) 2.64 (m, 1H) 1.01-0.86 (m, 8H) LCMS m/z (M+H) 402.2.

후처리

  1. customThe reaction mixture was quenched with 2 ml of water and 3 ml of DCM
  2. customthe organic phase separated
  3. concentrationThe organic phase was concentrated
  4. customthe residue purified by prep basic HPLC

출처 및 근거

ORD 기록
ord-d1226a04fb9d4fe4a3c674fdb3500300
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507521B2

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